Advertisement

Agents and Actions

, Volume 34, Issue 1–2, pp 274–277 | Cite as

Structural and functional organization of the human neutrophil 60 kDa bactericidal/permeability-increasing protein

  • C. E. Ooi
  • J. Weiss
  • P. Elsbach
C. Gordon van Arman Scholarship Competition (Finalists)

Abstract

We have isolated, after limited proteolysis of the bactericidal/permeability-increasing protein (BPI) of human polymorphonuclear leukocytes (PMN), two fragments representing roughly the two halves of the BPI molecule. The 25 kDa N-terminal fragment possesses all the antibacterial activities of the 60 kDa parent protein, while the ca. 30 kDa C-terminal fragment has no detectable activity. The 25 kDa fragment is as potent on a molar basis as holo-human BPI against roughEscherichia coli, is more potent than holo-BPI against more resistant smoothE. coli, and retains the specificity of BPI toward Gram-negative bacteria. The findings suggest that all of the molecular determinants of the antibacterial properties of BPI reside within the N-terminal half of the molecule, implying a novel structural/functional organization for a cytotoxic protein.

Keywords

Antibacterial Activity Human Neutrophil Antibacterial Property Polymorphonuclear Leukocyte Functional Organization 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. [1]
    P. Elsbach,Trends in biotechnology, 8, 26–30 (1990).CrossRefPubMedGoogle Scholar
  2. [2]
    P. Elsbach and J. Weiss,In inflammation: Basic principles and clinical correlates (Eds. J. L. Gallin, I. M. Golstein and R. Snyderman), pp. 445–470, Raven Press (1988).Google Scholar
  3. [3]
    J. E. Gabay et al.,Antibiotic proteins of human polymorphonuclear leukocytes. Proc. Natl. Acad. Sci., USA86, 5610–5614 (1989).Google Scholar
  4. [4]
    J. Weiss, P. Elsbach, I. Olsson and H. Odeberg,Purification and characterization of a potent bactericidal and membrane active protein from the granules of human polymorphonuclear leukocytes. J. Biol. Chem.253, 2664–2672 (1978).PubMedGoogle Scholar
  5. [5]
    P. Elsbach, J. Weiss, R. C. Franson, S. Beckerdite-Quagliata, A. Schneider and L. Harris,Separation and purification of a potent bactericidal/permeability-increasing protein and a closely associated phospholipase A2 from rabbit polymorphonuclear leukocytes. J. Biol. Chem.254, 11000–11009 (1979).PubMedGoogle Scholar
  6. [6]
    B. A. Mannion, J. Weiss and P. Elsbach,Separation of sublethal and lethal effects of the bactericidal/permeability-increasing protein on Escherichia coli. J. Clin. Invest.85, 853–860 (1990).PubMedGoogle Scholar
  7. [7]
    C. E. Ooi, J. Weiss, P. Elsbach, B. Frangione and B. A. Mannion,A 25 kDa NH 2-fragment carries all the antibacterial activities of the human neutrophil 60 kDa bactericidal/permeability-increasing protein. J. Biol. Chem.262, 14891–14894 (1987).PubMedGoogle Scholar
  8. [8]
    B. A. Mannion, E. S. Kalatzis, J. Weiss and P. Elsbach,Preferential binding of the neutrophil granule-derived bactericidal/permeability-increasing protein to target bacteria. J. Immunol142, 2807–2812 (1989).PubMedGoogle Scholar
  9. [9]
    U. K. Laemmli,Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature227, 680–685 (1970).PubMedGoogle Scholar
  10. [10]
    O. H. Lowry, N. J. Rosenbrough, A. L. Farr and R. J. Randall,Protein measurement with the Folin phenol reagent. L. Biol. Chem.193, 265–275 (1951).Google Scholar
  11. [11]
    P. W. Gray, G. Flaggs, S. R. Leong, R. J. Gumina, J. Weiss, C. E. Ooi and P. Elsbach,Cloning of the cDNA of a human neutrophil bactericidal protein. J. Biol. Chem.264, 9505–9509 (1989).PubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag 1991

Authors and Affiliations

  • C. E. Ooi
    • 1
  • J. Weiss
    • 1
  • P. Elsbach
    • 1
  1. 1.Departments of Medicine and MicrobiologyNew York University School of MedicineNew York

Personalised recommendations